Endoplasmic reticulum stress in the cellular release of damage-associated molecular patterns

Abstract Several pathological and inflammatory disorders induce a cytoprotective endoplasmic reticulum (ER) stress that aims at reestablishing tissue homeostasis, yet can also ignite lethal signaling pathways leading to apoptotic cell death when ER stress endures. Cells that undergo episodes of ER stress in response to pathological malfunction or cytotoxic agents can expose and release immunomodulatory damaged-associated molecular patterns (DAMPs) on their surface and into the extracellular space, respectively. Immunosuppressive DAMPs inhibit the transfer of antigens from stressed cells to antigen-presenting cells (APCs), whereas immunostimulatory DAMPs can act on APCs to facilitate antigen uptake, processing and presentation to stimulate T cell-mediated adaptive immune responses. In this review, we focus on immunomodulatory DAMPs that are released/exposed in conditions of ER stress induced in the context of chronic pathologies and anticancer therapies.